Publisher Summary This chapter describes the methods for studying the adhesion of microorganisms to intestinal mucus, intestinal tissue culture cells, and intestinal mucosal tissue pieces. Although intestinal mucus and tissue culture cells provide convenient models for different parts of the mucosa, whole intestinal tissue probably provides the most realistic substratum for the study of adhesion to the intestinal mucosa. Tissue pieces can also be obtained from different parts of the intestine, which allows for studying possible site specific adhesion. In the case of tissue from human origin, it will usually be diseased tissue, though some healthy tissue is often resected together with this. Thus, the effect of different diseases on adhesion can be studied as well. Moreover, the effect of the normal microbiota present on the intestinal mucosa can be taken into account as well. A potential disadvantage with the use of tissue pieces, especially from human origin, may be the restricted availability and the requirement of immediate processing when available. The chapter also discusses how to determine the affinity of microorganisms for substrata and the maximum number of binding sites available on a substratum.